The new imaging technique, is based on the recognition of calcium ions in neurons, and could track the way brain circuits perform such functions, like detecting an odor or instigating movement.
Previous research has shown us that brain imaging can lead to detection of psychiatric disorders like autism. MEG machines have been used to analyze the magnetic fields of a children's brains.
Senior author Guoping Feng, and his associates, whose paper was published in Neuron, say:
"To understand psychiatric disorders we need to study animal models, and to find out what's happening in the brain when the animal is behaving abnormally. This is a very powerful tool that will really help us understand animal models of these diseases and study how the brain functions normally and in a diseased state."
All types of brain function need many different neurons in separate parts of the brain to exchange information with each other. They reach this communication by sending electrical signals, prompting an influx of calcium ions into active cells.
The researchers used dye that binds to calcium, to take images of the neural activity in neurons. Although the brain has thousands of cell types, each with their own function, the dye is absorbed by all cells, regardless of type, making it unachievable to identify calcium in specific cell types using this approach.
To bypass this problem, the MIT-lead research team made a calcium-imaging system that aims at specific cell types, using a a green fluorescent protein (GFP). GFP was first produced by Junichi Nakai of Saitama University in Japan, and became active when binding with calcium. Loren Looger of the Howard Hughes Medical Institute, an author of the current paper, then modified the protein giving it a strong enough signal for use in living animals.
The investigators then genetically engineered mice to demonstrate this protein in a type of neuron know as pyramidal cells, by matching the gene with a regulatory DNA pattern that is only active in those cells.
Using two-photon microscopy to envision the cells at high speed and high resolution, the researchers were able to pinpoint pyramidal cells that are active while the brain is engaging in a certain task, or answering to a specific stimulus.
In this particular study, the authors were able to identify the cells in the somatosensory cortex that start working at the time a mouse's whiskers are touched, as well as olfactory cells that respond to certain smells.
The team is now developing mice that demonstrate the calcium-sensitive proteins, and also show symptoms of obsessive-compulsive disorder and autistic behavior. They will then use these mice to search for neuron firing cycles that differ from those of normal mice. This may assist in figuring out exactly what goes wrong at the cellular level, providing insight in physical terms about these diseases.
"Right now, we only know that defects in neuron-neuron communications play a key role in psychiatric disorders. We do not know the exact nature of the defects and the specific cell types involved. If we knew what cell types are abnormal, we could find ways to correct abnormal firing patterns."
The MIT team plans on collaborating their imaging technology with optogenetics, allowing them to use light, to turn on and off, certain classes of neurons.
By triggering certain cells and then watching the response in target cells, they can accurately chart brain circuits.
Written by Kelly Fitzgerald